MS Team Breaks into Cancer Immunotherapy

As a longtime researcher into multiple sclerosis, Howard Weiner, MD, never thought he would publish a paper on cancer immunotherapy—let alone help to start a new company dedicated to developing cancer therapeutics.

But that is exactly what happened thanks to an idea that sparked from the cross-disciplinary interactions between Dr. Weiner and his fellow researchers at the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital (BWH) and a meeting at a holiday party with a member of the Partners Innovation team.

The result of this fortunate and somewhat unexpected series of events is Tilos Therapeutics, a new PHS spinoff company seeded by Partners Innovation Fund (PIF) and the Boehringer Ingelheim Venture Fund. The Cambridge-based company is now working to take the science that started in Weiner’s lab and modifying it further for study in humans.

How did a research team specializing in neurological disorders end up targeting cancer instead of multiple sclerosis? The connection between the two diseases can be found in their effects on regulatory T cells, a type of white blood cell responsible for directing the body’s immune response and protecting healthy cells from being attacked.

Multiple sclerosis is an immune-mediated disease in which the body’s immune cells periodically attack the central nervous system, damaging the myelin sheaths that protect nerve cells in the brain and spinal cord. During an attack, scientists have observed a decrease in the functioning of regulatory T cells, suggesting that the cells are not doing enough to prevent immune cells from attacking healthy nerve cells.

In cancer, conversely, these regulatory T cells tend to be overactive, which leads them to suppress the body’s defense against attacking cancer cells, allowing tumors to grow unchecked. The field of cancer immunotherapy is dedicated to finding strategies to override tumor cells’ ability to hide from immune cells.

In a project led by Galina Gabriely, PhD, a postdoctoral researcher in Weiner’s lab, the team used antibodies they developed earlier to target a complex on the surface of regulatory T cells that expresses latency-associated peptide (LAP), the chemical signal that inhibits immune response.

In mouse models of glioblastoma (brain tumors), melanoma and colorectal cancer, the team demonstrated that these LAP antibodies could be used to override the immune-suppressant capabilities of tumor cells and prompt the immune system to mount a counteroffensive. The work was detailed in a paper in Science Immunology.

Jay Knowles, a partner with the Partners Innovation Fund (PIF), first heard about the team’s work while talking to Dr. Weiner at a holiday party in late 2014.

Intrigued by the concept, Knowles arranged a formal meeting with Weiner and the Partners Innovation team in early 2015. Knowles then connected with Martin Heidecker from the Boehringer Ingelheim Venture Fund, and the seeds for collaboration were planted.

In the spring of 2016, PIF hired Barbara Fox, PhD, as Entrepreneur-in-Residence. As she reviewed the projects in the PIF pipeline, the proposal by Dr. Weiner’s team immediately stood out.

“As an immunologist, it is very exciting to see the recent breakthroughs in the field as investigators have figured out how to effectively focus the immune response onto tumors,” Fox said.

“Yet, many challenges remain and many patients cannot yet be treated with the current therapies. The anti-LAP antibodies have the potential to break through many of the current obstacles, transforming cancer treatment for multiple tumor types.”

Tilos Therapeutics launched in August of 2016 with Fox as Director and CEO. Heidecker, Knowles and Roger Kitterman, Vice President, Venture and Managing Partner of PIF, are also Directors.

“If there’s a lesson learned [from this project], it’s that you never know where an idea is going to come from,” Knowles said. The larger message to the research community is that the Partners Innovation Fund is open for business, he added. “We are looking for opportunities to invest.”

While launching Tilos, Dr. Weiner, wrote and directed the “Last Poker Game” which premiered at the TriBeCa Film Festival in April and stars Martin Landau and Paul Sorvino.